Many optically active compounds are made from common, commercially available raw materials via organic syntheses which produce the racemic mixture of two optically active enantiomorphs, which then has to be separated by difficult procedures to recover the desired enantiomorph in pure form. This separation method is frequently one of the most complex parts of the synthesis operation, since the optical isomers have identical physical and chemical properties, except vis-a-vis other optical isomers.
A well-known technique for achieving this separation is to use supersaturation of the racemic mixture, either in the form of a melt, or of a solution in a solvent, and then crystallizing out only the desired enantiomorph by seeding the supersaturated system with crystals of the desired isomer. Supersaturation is achieved by preparing a saturated solution or melt of the racemic mixture, and then carefully subcooling this system to avoid spontaneous crystallization of both enantiomorphs. The degree of subcooling which can be achieved is obviously a function of the stability of the supersaturated system against spontaneous crystallization, of the presence of nucleating particles which could bring about spontaneous crystallization, and of the method of cooling the saturated solution. Wall or coil cooling introduces regions of low temperature where spontaneous crystallization can occur, and vigorous agitation can have the same undesirable effect. The degree of subcooling which can be reached is important in determining the yield of desirable isomer which can be achieved when the supersaturated system is seeded with crystals of that material. Obviously, a high degree of supercooling will result in a higher yield of desirable optical isomer per pass than only a small degree of subcooling.
Rather than lowering the temperature by withdrawing heat from a saturated system to enter the supersaturated domain, it is possible to bring this about by an adiabatic increase in the pressure on the system. This is due to the fact that the melting point of a substance increases with pressure, provided there is an increase in molar volume when the substance melts. Therefore, as the pressure of a saturated mixture, either a melt or a solution, is increased, the melting point of the constituents increases, and crystallization will occur. However, in many cases, this crystallization will be delayed, as the pressure is increased, resulting in a supersaturated system. Since the pressure on a system can be applied uniformly and gradually, without gradients and agitation, supersaturation is more likely and more extensive than in a thermal cycle. It will also permit using the selective seeding technique to systems which do not exhibit any or sufficient supercooling when the temperature is lowered.